Search Results (708)

In order to improve the inversion accuracy of electrical resistivity tomography (ERT) and overcome the limitations of traditional linear methods, this paper proposes an improved shuffled frog leaping algorithm (SFLA). First, an equilibrium grouping strategy is designed to balance the contribution weight of each subgroup to the global optimal solution, suppressing the local optimum traps caused by the dominance of high-quality groups. Second, an adaptive movement operator is constructed to dynamically regulate the step size of the search, enhancing the guiding effect of the optimal solution. In synthetic data tests of three typical electrical models, including a high-resistivity anomaly with 5% random noise, a normal fault, and a reverse fault, the improved algorithm shows an approximately 2.3 times higher accuracy in boundary identification of the anomaly body compared to the least squares (LS) method and standard SFLA. Additionally, the root mean square error is reduced by 57%. In the engineering validation at the Baota Mountain mining area in Jurong, the improved SFLA inversion clearly reveals the undulating bedrock morphology. At a measuring point 55 m along the profile, the bedrock depth is 14.05 m (ZK3 verification value 12.0 m, error 17%), and at 96 m, the depth is 6.9 m (ZK2 verification value 6.7 m, error 3.0%). The characteristic of deeper bedrock to the south and shallower to the north is highly consistent with the terrain and drilling data (RMSE = 1.053). This algorithm provides reliable technical support for precise detection of complex geological structures using ERT. Full article

This study proposes an integrated, machine learning-based multi-objective optimization framework to evaluate and optimize the utilization of steel slag in road base layers, simultaneously addressing economic costs and environmental impacts. A comprehensive dataset of 482 scenarios was engineered based on literature-informed parameters, encompassing transport distance, processing energy intensity, initial moisture content, gradation adjustments, and regional electricity emission factors. Four advanced tree-based ensemble regression algorithms—Random Forest Regressor (RFR), Extremely Randomized Trees (ERTs), Gradient Boosted Regressor (GBR), and Extreme Gradient Boosting Regressor (XGBR)—were rigorously evaluated. Among these, GBR demonstrated superior predictive performance (R² > 0.95, RMSE < 7.5), effectively capturing complex nonlinear interactions inherent in slag processing and logistics operations. Feature importance analysis via SHapley Additive exPlanations (SHAP) provided interpretative insights, highlighting transport distance and energy intensity as dominant factors affecting unit cost, while moisture content and grid emission factor predominantly influenced CO₂ emissions. Subsequently, the Gradient Boosted Regressor model was integrated into a Non-Dominated Sorting Genetic Algorithm II (NSGA-II) framework to explore optimal trade-offs between cost and emissions. The resulting Pareto front revealed a diverse solution space, with significant nonlinear trade-offs between economic efficiency and environmental performance, clearly identifying strategic inflection points. To facilitate actionable decision-making, the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method was applied, identifying an optimal balanced solution characterized by a transport distance of 47 km, energy intensity of 1.21 kWh/ton, moisture content of 6.2%, moderate gradation adjustment, and a grid CO₂ factor of 0.47 kg CO₂/kWh. This scenario offered a substantial reduction (45%) in CO₂ emissions relative to cost-minimized solutions, with a moderate increase (33%) in total cost, presenting a realistic and balanced pathway for sustainable infrastructure practices. Overall, this study introduces a robust, scalable, and interpretable optimization framework, providing valuable methodological advancements for sustainable decision making in infrastructure planning and circular economy initiatives. Full article

Pompe disease is a rare autosomal-recessive neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to the pathological accumulation of glycogen and impaired autophagy. Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) has been available since 2006, but may lead to the formation of anti-drug antibodies (ADAs) against the recombinant human enzyme, which, in turn, may adversely affect the response to ERT. Knowledge of the antigenic determinants of rhGAA involved in interaction with ADAs may facilitate the development of strategies to attenuate the anti-drug immune response in patients. Here, we determined the rhGAA ADA epitopes in the plasma of Pompe disease patients using a series of affinity purifications combined with epitope extraction and label free quantitation LC-MS. Full article

The present paper deals with an inhabited, creeping mountainous landmass with profound surface deformation that affects the local community. The scope of the paper is to gather surficial and subsurface information in order to understand the parameters of this creeping mass, which is usually affected by several parameters, such as its geometry, subsurface water, and shear zone. Therefore, a combined aerial and surface investigation has been conducted. The aerial investigation involves UAV’s LiDAR acquisition for the terrain model and a comparison of historical aerial photographs for land use changes. The multi-technique surface investigation included resistivity (ERT) and seismic (SRT, MASW) measurements and density determination of geological formations. This combination of methods proved to be fruitful since several aspects of the landslide were clarified, such as water flow paths, the internal geological structure of the creeping mass, and its geometrical extent. The depth of the shear zone of the creeping mass is delineated at the first five to ten meters from the surface, especially from the difference in diachronic resistivity change. Full article

Gaucher disease (GD) is an autosomal recessive disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) remains the standard of care for non-neuropathic GD patients, its high cost significantly limits accessibility. To enhance production efficiency, we developed a lentiviral system encoding a codon-optimized GCase gene driven by the human elongation factor 1a (hEF1α) promoter for stable production in human cell lines. A functional lentiviral vector, LV_EF1α_GBA_Opt, was generated at a titer of 7.88 × 10⁸ LV particles/mL as determined by qPCR. Six transduction cycles were performed at a multiplicity of infection of 30–50. The transduced heterogeneous human cell population showed GCase-specific activity of 307.5 ± 53.49 nmol/mg protein/h, which represents a 3.21-fold increase compared to wild-type 293FT cells (95.58 ± 16.5 nmol/mg protein/h). Following single-cell cloning, two clones showed specific activity of 763.8 ± 135.1 and 752.0 ± 152.1 nmol/mg/h (clones 15 and 16, respectively). These results show that codon optimization, a lentiviral delivery system, and clonal selection together enable the establishment of stable human cell lines capable of producing high levels of biologically active, synthetic recombinant GCase in vitro. Further studies are warranted for the functional validation in GD patient-derived fibroblasts and animal models. Full article

The increasing demand for high-resolution subsurface imaging has driven significant advances in geophysical inversion methodologies. Despite the availability of various software packages for electrical resistivity tomography (ERT), time-domain induced polarization (TDIP), and seismic refraction tomography (SRT), significant challenges remain in selecting optimal regularization parameters and in the effective incorporation of prior information into the inversion process. In this study, we propose new strategies to address these critical issues by developing versatile and flexible tools for electrical and seismic tomographic data inversion. Specifically, we introduce two automated procedures for regularization parameter selection: a full loop method (fixed-λ optimization) where the regularization parameter is kept constant during the inversion process, and a single-inversion approach (automaticLam) where it varies throughout the iterations. Additionally, we present a novel constrained inversion strategy that effectively balances prior information, minimizes data misfit, and promotes model smoothness. This approach is thoroughly compared with the state-of-the-art methods, demonstrating its superiority in maintaining model reliability and reducing dependence on subjective operator choices. Applications to synthetic, laboratory, and real-world case studies validate the efficacy of our strategies, showcasing their potential to enhance the robustness of geophysical models and standardize the inversion process, ensuring its independence from operator decisions. Full article

Objectives: This systematic literature review aimed to identify studies assessing the clinical efficacy and real-world effectiveness of current and emerging treatments for Fabry disease. Methods: Searches of the MEDLINE, EMBASE, and Cochrane library databases, as well as relevant congress proceedings, were conducted to identify publications reporting on studies in patients of any age, sex, race, or ethnicity who received any approved or experimental treatment for Fabry disease, published before 17 June 2024. Results: Of 1881 publications screened, 234 reported data on renal, cardiac, cerebrovascular, and disease severity outcomes from 225 studies. The majority of reported studies were observational in nature (n = 150; 67%) and involved only adults (n = 172; 74%). Study designs and patient populations were highly heterogeneous, and cross-study conclusions about the effectiveness of different therapies could not be made. Enzyme replacement therapy (ERT) with agalsidase alfa or agalsidase beta stabilized renal function and cardiac structure in patients with Fabry disease. Early initiation of ERT in childhood or young adulthood was associated with better renal and cardiac outcomes than treatment initiation at a later age. The small number of comparator studies of agalsidase alfa and agalsidase beta suggested similar efficacy. Patients treated with migalastat and pegunigalsidase alfa also maintained stable renal function and cardiac structure. Conclusions: Overall, current treatments slow the progression of renal and cardiac decline in patients with Fabry disease. Large cohort studies with long-term follow-up and baseline stratification based on clinical phenotype are needed to address evidence gaps and provide clinicians with robust data to inform treatment decisions. Full article

The possibility of collecting new archaeological elements useful in reconstructing the dynamics of population, production and commercial activities in the Bronze Age at the edge of the central-southern Venice Lagoon was provided between 2023 and 2024 thanks to an intervention of rescue archaeology planned during some water restoration works in the Giare–Mira area. Three small excavations revealed, approximately one meter below the current surface and covered by alluvial sediments, a rather complex palimpsest dated to the late Recent and the early Final Bronze Age. Three large circular pits containing exclusively purified grey/blue clay and very rare inclusions of vegetable fibres, and many large, fired clay vessels’ bases, walls and rims clustered in concentrated assemblages and random deposits point to potential on-site production. Two pyro-technological structures, one characterised by a sub-circular combustion chamber and a long inlet channel/praefurnium, and the second one with a sub-rectangular shape with arched niches along its southern side, complete the exceptional context here discovered. To analyse the relationship between the site and the natural sedimentary succession and to evaluate the possible extension of this site, three electrical resistivity tomography (ERT) and low-frequency electromagnetic (FDEM) measurements were collected. Several manual core drillings associated with remote sensing integrated the geophysical data in the analysis of the geomorphological evolution of this area, clearly related to different phases of fluvial activity, in a framework of continuous relative sea level rise. The typology and chronology of the archaeological structures and materials, currently undergoing further analyses, support the interpretation of the site as a late Recent/early Final Bronze Age productive site. Geophysical and geomorphological data provide information on the palaeoenvironmental setting, suggesting that the site was located on a fine-grained, stable alluvial plain at a distance of a few kilometres from the lagoon shore to the south-east and the course of the Brenta River to the north. The archaeological site was buried by fine-grained floodplain deposits attributed to the Brenta River. The good preservation of the archaeological structures buried by fluvial sediments suggests that the site was abandoned soon before sedimentation started. Full article

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder causing systemic skeletal dysplasia due to a deficiency of N-acetyl-galactosamine-6-sulfate sulfatase (GALNS) enzyme activity, leading to the impaired degradation and accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate. While treatments such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available, they have significant limitations regarding efficacy in skeletal tissues and long-term safety, highlighting the need for more effective therapies. We evaluated a novel gene therapy approach using a dual Integrase-deficient lentiviral vector (IDLV) to deliver an expression cassette that includes human GALNS cDNA and Cas9 sgRNA, targeting the upstream region of the mouse Galns initial codon. This approach leverages the endogenous promoter to drive transgene expression. We assessed in vitro transduction, editing, and functional correction in NIH3T3 and MPS IVA mouse fibroblasts. In vivo efficacy was successfully evaluated via the facial vein injection in MPS IVA newborn mice. In vitro, this IDLV platform demonstrated supraphysiological GALNS activity in cell lysate, resulting in the normalization of KS levels. In vivo direct IDLV platform in newborn MPS IVA mice led to sustained plasma GALNS activity, reduced plasma KS, and favorable biodistribution. Partial correction of heart and bone pathology was observed, with no vector toxicity and minimal antibody responses. This dual IDLV-CRISPR/Cas9 approach effectively mediated targeted GALNS knock-in, yielding sustained enzyme activity, reduced KS storage, and partial pathological amelioration in MPS IVA mice. In conclusion, IDLVs represent an efficient, safe platform for delivering the CRISPR/Cas9 gene editing system for MPS IVA. Full article

Background/Objectives: For those with comorbid mild traumatic brain injury/post-traumatic stress disorder (mTBI/PTSD), deficits are common with regard to recognition of emotion expression in others. These deficits can cause isolation and suicidal ideation. For mTBI/PTSD, there is a dearth of information regarding effective treatment. In pilot work, we developed and tested an innovative treatment to improve recognition of both affect (facial expression of emotion) and prosody (spoken expression of emotion). Methods: We enrolled eight Veterans with mTBI/PTSD and administered eight treatment sessions. Measures included the following: Florida Affect Battery (FAB), a test of emotion recognition of facial affect and spoken prosody; Attention Index of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); and Emotion Recognition Test (ERT), a speed test of facial emotion recognition. Results: There was a significant treatment response according to the FAB (p = 0.01, effect size = 1.2); RBANS attention index (p = 0.04, effect size = 0.99); and trending toward significance for the ERT (0.17, effect size 0.75). Participants were able to engage actively in all eight sessions and provided qualitative evidence supporting generalization of the training to interpersonal relationships. Conclusions: Our data show promising clinical potential and warrant future research, given the importance of developing novel interventions to train and restore recognition of emotion in Veterans with mTBI/PTSD. Full article

Lysosomal storage disorders (LSDs) constitute a group of monogenic systemic diseases resulting from deficiencies in specific lysosomal enzymes that cause the intralysosomal accumulation of non- or partially degraded substrates, leading to lysosomal dysfunction. In some cases of LSDs, the bone is more severely affected, thus producing skeletal manifestations in patients. Current therapies, such as enzyme replacement therapy (ERT) and gene therapy (GT), show limited efficacy in correcting skeletal abnormalities. Increasing evidence suggests that microenvironmental disturbances also contribute significantly to disease pathogenesis. Therefore, therapeutic strategies targeting lysosomal dysfunction and microenvironmental dysregulation are needed. Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are emerging as promising candidates in regenerative medicine due to their immunomodulatory, pro-regenerative, and paracrine properties. MSC-EVs have shown potential to modulate the microenvironment and favor tissue repair in bone-related disorders such as osteoarthritis and osteoporosis. Interestingly, MSC-EVs can be engineered to reach the bone and carry therapeutics, including ERT- and GT-related molecules, enabling targeted delivery to hard-to-reach bone regions. This review describes the main features of MSC-EVs and discusses the therapeutic potential of MSC-EVs as a potential cell-free strategy for bone-affected LSDs. Full article

With the continuous expansion of users, businesses, and services in electricity retail trading systems, the demand for personalized recommendations has grown significantly. To address the issue of reduced recommendation accuracy caused by insufficient data in standalone recommendation systems, the academic community has conducted in-depth research on distributed recommendation systems. However, this collaborative recommendation environment faces two critical challenges: first, how to effectively protect the privacy of data providers and power users during the recommendation process; second, how to handle the potential presence of malicious data providers who may supply false recommendation data, thereby compromising the system’s reliability. To tackle these challenges, a blockchain-based lightweight reputation-aware electricity retail trading service recommendation (BLR-ERTS) system is proposed, tailored for electricity retail trading scenarios. The system innovatively introduces a recommendation method based on Locality-Sensitive Hashing (LSH) to enhance user privacy protection. Additionally, a reputation management mechanism is designed to identify and mitigate malicious data providers, ensuring the quality and trustworthiness of the recommendations. Through theoretical analysis, the security characteristics and privacy-preserving capabilities of the proposed system are explored. Experimental results show that BLR-ERTS achieves an MAE of 0.52, MSE of 0.275, and RMSE of 0.52 in recommendation accuracy. Compared with existing baseline methods, BLR-ERTS improves MAE, MSE, and RMSE by approximately 13%, 14%, and 13%, respectively. Moreover, the system exhibits 94% efficiency, outperforming comparable approaches by 4–24%, and maintains robustness with only a 30% attack success rate under adversarial conditions. The findings demonstrate that BLR-ERTS not only meets privacy protection requirements but also significantly improves recommendation accuracy and system robustness, making it a highly effective solution in a multi-party collaborative environment. Full article

Melatonin (MT) has been reported to alleviate chilling injury (CI) in postharvest tomato fruit during low-temperature storage. In the present study, the DNA methylation profile changes in the CpG islands of ethylene signaling genes regulated by MT in postharvest tomato fruit during low-temperature storage were detected. The MT treatment increased the content of total soluble solids (TSS) and enhanced the ethylene production of tomato fruit. Moreover, it decreased titratable acidity (TA) content, inhibited the activity of polygalacturonase (PG), and kept the firmness of tomato fruit under low-temperature storage. In the MT-treated tomato fruit, significant changes in DNA methylation of CpG island of SlACS10, LeCTR1, LeEIN3, SlERF-A1, and LeERT10 genes were induced; the expression of LeCTR1 was inhibited; and the expression of SlACS10, LeEIN3, and SlERF-A1 genes was increased, by which the ethylene signaling might be influenced and the CI was alleviated. The present results provide evidence that the CI of postharvest tomato fruit alleviated by MT might be related to the changes in DNA methylation of ethylene-signaling genes. Full article

To address the challenges in identifying NAPL contamination within low-permeability clay sites, this study innovatively integrates high-density electrical resistivity tomography (ERT) with a UNet deep learning model to establish an intelligent contamination detection system. Taking an industrial site in Shanghai as the research object, we collected apparent resistivity data using the WGMD-9 system, obtained resistivity profiles through inversion imaging, and constructed training sets by generating contamination labels via K-means clustering. A semantic segmentation model with skip connections and multi-scale feature fusion was developed based on the UNet architecture to achieve automatic identification of contaminated areas. Experimental results demonstrate that the model achieves a mean Intersection over Union (mIoU) of 86.58%, an accuracy (Acc) of 99.42%, a precision (Pre) of 75.72%, a recall (Rec) of 76.80%, and an F1 score (f1) of 76.23%, effectively overcoming the noise interference in electrical anomaly interpretation through conventional geophysical methods in low-permeability clay, while outperforming DeepLabV3, DeepLabV3+, PSPNet, and LinkNet models. Time-lapse resistivity imaging verifies the feasibility of dynamic monitoring for contaminant migration, while the integration of the VGG-16 encoder and hyperparameter optimization (learning rate of 0.0001 and batch size of 8) significantly enhances model performance. Case visualization reveals high consistency between segmentation results and actual contamination distribution, enabling precise localization of spatial morphology for contamination plumes. This technological breakthrough overcomes the high-cost and low-efficiency limitations of traditional borehole sampling, providing a high-precision, non-destructive intelligent detection solution for contaminated site remediation. Full article

Eliglustat (Cerdelga^®) is a potent and specific inhibitor of the enzyme glucosylceramide synthase and serves as a substrate reduction therapy for adult patients with Gaucher disease type 1 (GD1). It prevents the accumulation of several lipids, including glucosylsphingosine (also known as Lyso-Gb1). In addition to its role in diagnostics, Lyso-Gb1 has been proven to be a reliable biomarker for assessing disease severity and monitoring treatment efficacy. We present the case of an obese, splenectomized GD1 patient on long-term enzyme replacement therapy (ERT) who reported worsening fatigue and showed a progressive increase in Lyso-Gb1 levels after switching treatment from ERT to eliglustat. We provide a discussion of the potential clinical factors contributing to this outcome. As seen with ERT, Lyso-Gb1 levels during eliglustat treatment appear to respond earlier than other biochemical and clinical parameters. An increase in Lyso-Gb1 may signal early compromised clinical efficacy of the treatment. Data on biochemical and clinical outcomes in splenectomized or obese patients treated with eliglustat are limited, and the role of specific genotypes requires further clarification. The variability in responses to eliglustat highlights the complexity of GD and underscores the need for personalized approaches to treatment and monitoring. Full article